Scientists break down brain barriers to address tumors

The brain is a kind of strength, equipped with barriers designed to avoid dangerous pathogens. But protection comes at a cost: these barriers interfere with the immune system when faced with serious threats such as glioblastoma, a deadly brain tumor for which there are few effective treatments.

Yale researchers have found a new way to bypass the brain’s natural defenses when they are counterproductive by sliding rescuers from the immune system through the fortress drainage system, report January 15 in the journal. Nature.

People had thought that the immune system could do very little to fight brain tumors, ”said lead author and correspondent Akiko Iwasaki. “There has been no way for glioblastoma patients to benefit from immunotherapy.”

Iwasaki is a professor of immunobiology at Waldemar Von Zedtwitz and a professor of molecular, cellular and developmental biology, and a researcher at the Howard Hughes Medical Institute.

While the brain itself does not have a direct way to eliminate cellular debris, the small vessels that line the inside of the skull collect tissue waste and remove it through the body’s lymphatic system, which filters toxins and debris from the body. Body. It is this elimination system that the researchers exploited in the new study.

These vessels form shortly after birth, stimulated in part by the gene known as vascular endothelial growth factor C or VEGF-C.

Jean-Leon Thomas de Yale, associate professor of neurology at Yale and co-lead author of the article, wondered if VEGF-C could increase the immune response if lymphatic drainage increased. And lead author Eric Song, a student working in the Iwasaki laboratory, wanted to see if VEGF-C could be used specifically to increase the surveillance of the glioblastoma tumor immune system. Together, the team investigated whether the introduction of VEGF-C through this drainage system would specifically attack brain tumors.

The team introduced VEGF C into the cerebrospinal fluid of mice with glioblastoma and observed a higher level of T-cell response to tumors in the brain. When combined with immune system control point inhibitors commonly used in immunotherapy, treatment with VEGF-C significantly prolongs the survival of mice. In other words, the introduction of VEGF-C, along with cancer immunotherapy drugs, was apparently enough to attack brain tumors.

These results are remarkable, ”said Iwasaki. “We would like to take this treatment to patients with glioblastoma. The prognosis with current surgery and chemotherapy therapies is still very bleak. “

Reference: Song, et al. (2020) VEGF-C-driven lymphatic drainage allows immunovigilance of brain tumors. Nature DOI: 10.1038 / s41586-019-1912-x

This article has been reissued from the following materials. Note: the material may have been edited for length and content. For more information, contact the source cited.

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